Oral drug delivery is a multifaceted challenge, and a molecule of interest faces substantial barriers to achieve systemic circulation via the bloodstream or the lymphatic system. It is estimated that 50% of drugs in development fail due to unfavorable oral bioavailability. One barrier is mucus, which has largely been ignored or poorly modeled by most in-vitro systems to date. Nanocarriers and molecular species can be trapped in mucus due to steric obstruction as well as binding interactions with the mucin fibers that formulate the mesh-like structure of the mucus network. The observation that native milk emulsion droplets are coated in mucins and are highly effective in delivery of a variety of types of molecular cargo motivates exploration of the potential role of the mucin coating. This work describes the impact of the incorporation of mucin on transport of colloidal particles. Diffusion coefficients of nanoparticles with EDC-NHS crosslinked mucin were measured to understand the effect of mucin as a biomaterial for oral delivery formulations. This coating was compared to additional commonly used polymers in oral drug delivery coating. Multiple particle tracking experiments were conducted to characterize muco-adhesive or muco-diffusive characteristics of particles with and without incorporated mucins to gain a deeper understanding of how mucins may impact efficiency of nanoparticle movement through the mucus layer. Mucin-crosslinked particles exhibited increased diffusion coefficients in exogenous porcine mucus, suggesting a modulatory role of mucin in nanoparticle transport. Investigating the effects of exogenous mucin will help lead to understanding mucus-particle interactions, informing the design of effective muco-adhesive or muco-diffusive drug delivery systems.
